Male subjects with hemophilia A (FVIII:C =2% confirmed at screening), previously treated with = 150 exposure days to any Factor VIII product, undergoing elective major surgery that is anticipated to require FVIII infusions over a period of at least 6 days following surgery MedDRA version: 8.1 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII
Conditions
Interventions
Product Name: ReFacto AF
Product Code: 3082B2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: moroctocog alfa
CAS Number: 284036/24/4
Current Sponsor code: 3082
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals, Inc. Clinical Research and Development
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Male subjects with hemophilia A- FVIII:C = 2% - Age = 12 years - A negative FVIII inhibitor at both the local laboratory and central laboratory at screening - A negative past medical history of a FVIII inhibitor - Previously treated with = 150 exposure days to any Factor VIII product - The subject will be undergoing elective major surgery that is anticipated to require FVIII infusions and daily FVIII activity monitoring over a period of at least 6 days following surgery - ALT (SGOT) and AST (SGPT) =5.0 x ULN, and bilirubin =2mg/dL (33 µmol/L) - Serum albumin = LLN- Serum creatinine =1.25 x ULN- Platelet count = 100,000 /µL - Absolute CD4 count >200 µL - PT =1.25 x ULN or INR = 1.5 - Patients receiving therapy for HIV or Hepatitis infection, must be on a stable antiviral regimen at the time of study entry - The patient should be able to comply with the mandatory 72-hour washout period as specified in the protocol - The patient should be able to comply with the required inpatient length of stay including at least 2 days for BI subjects and at least 6 days for all CI subjects The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to inclusion criteria. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - A history of FVIII inhibitor (clinical or laboratory based assessment, as defined in the protocol definitions), such as recurrent low titer values. Any measured Bethesda inhibitor titer greater than or equal to 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay - Presence of a bleeding disorder in addition to hemophilia A - Treatment with any investigational drug or device within the past 30 days, except for subjects entering from other studies of ReFacto AF - Prior participation in this study (except for screen failures) - Regular (e.g. daily, QOD) use of antifibrinolytic agents or medications known to influence platelet function such as aspirin or certain NSAIDs - Concomitant therapy with immunosuppressive drugs (e.g., IVIG, routine systemic corticosteroids) - Known hypersensitivity to hamster protein - Unwilling or unable to follow the terms of the protocol The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstration of the safety and efficacy of ReFacto AF administered by bolus injection or continuous infusion during the perioperative management of patients with hemophilia A undergoing major surgery ;Secondary Objective: - Characterize and compare the total and daily dose of ReFacto AF for both bolus injection and continuous infusion - Characterize the pharmacokinetics of ReFacto AF in the patient population - Characterize the pharmacokinetic measurements required for surgical prophylaxis - Characterize the predicted and estimated actual blood loss and transfusion requirements in the study patient population - Characterize the variety of regimens used in those patients treated by continuous infusion - Characterize patient compliance with prescribed regimens in the outpatient setting;Primary end point(s): Efficacy: Assessment of hemostatic efficacy at the end of surgery as determined by the investigator and/or the surgeon using the 4 point ordinal scale below: a) Excellent – Achieved hemostasis comparable to that expected after similar surgery in a non-hemophilic subject b) Good – Prolonged time to hemostasis, with somewhat increased bleeding compared to that expected after similar surgery in a non-hemophilic subject c) Moderate – Obviously delayed hemostasis, but manageable with additional infusions of FVIII d) None – No hemostatic response Safety: evaluations will include routine physical and laboratory examinations, including assessment for FVIII inhibitor development, thrombosis and allergic reactions. All adverse events will be recorded | — |
Countries
France, Sweden
Outcome results
None listed